Premium
Aluminum fluoride inhibits phospholipase D activation by a GTP‐binding protein‐independent mechanism
Author(s) -
Li Liang,
Fleming Norman
Publication year - 1999
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(99)01196-5
Subject(s) - phospholipase d , gtp' , chemistry , biochemistry , fluoride , phosphatase , biophysics , phospholipid , membrane , biology , enzyme , inorganic chemistry
Aluminum fluoride (AlF 4 − ) inhibited guanine nucleotide‐activated phospholipase D (PLD) in rat submandibular gland cell‐free lysates in a concentration‐dependent response. This effect was consistent in permeabilized cells with endogenous phospholipid PLD substrates. Inhibition was not caused by either fluoride or aluminum alone and was reversed by aluminum chelation. Inhibition of PLD by aluminum fluoride was not mediated by cAMP, phosphatases 1, 2A or 2B, or phosphatidate phosphohydrolase. AlF 4 − had a similar inhibitory effect on rArf‐stimulated PLD, but did not block the translocation of Arf from cytosol to membranes, indicating a post‐GTP‐binding‐protein site of action. Oleate‐sensitive PLD, which is not guanine nucleotide‐dependent, was also inhibited by AlF 4 − , supporting a G protein‐independent mechanism of action. A submandibular Golgi‐enriched membrane preparation had high PLD activity which was also potently inhibited by AlF 4 − , leading to speculation that the known fluoride inhibition of Golgi vesicle transport may be PLD‐mediated. It is proposed that aluminum fluoride inhibits different forms of PLD by a mechanism that is independent of GTP‐binding proteins and that acts via a membrane‐associated target which may be the enzyme itself.